Study Linking Monsanto Corn to Cancer Must Be Taken Seriously by Regulators

by John Vidal

The Guardian UK, 29 Septembewr 2012

Trial suggesting a GM maize strain causes cancer has attracted a torrent of abuse, but it cannot be swept under the carpet.

Professor Gilles-Eric Séralini, professor of molecular biology at Caen university in France, knows how to inflame the GM industry and its friends. For seven years he and his team have questioned the safety standards applied to varieties of GM maize and tried to re-analyse industry-funded studies presented to governments.

The GM industry has traditionally reacted furiously and personally. Séralini has been widely insulted and smeared and last year, in some desperation, he sued Marc Fellous, president of the French Association of Plant Biotechnology, for defamation, and won (although he was only awarded a nominal €1 in damages).

But last week, Seralini brought the whole scientific and corporate establishment crashing down on his head. In a peer-reviewed US journal, Food and Chemical Toxicology, he reported the results of a €3.2m study. Fed a diet of Monsanto's Roundup-tolerant GM maize NK603 for two years, or exposed to Roundup over the same period, rats developed higher levels of cancers and died earlier than controls. Séralini suggested that the results could be explained by the endocrine-disrupting effects of Roundup, and overexpression of the transgene in the GMO.

Commentators variously claimed the study to be "biased", "poorly performed", "bogus", "fraudulent", "sub-standard", "sloppy agenda-based science", "inadequate" and "unsatisfactory". Séralini was said to have "sought harm" for the rats, the experiment was dismissed as "inhumane" and the research group was called "partisan". France was outed as "the most anti-science country in anti-science Europe" and vociferous GM supporters such as Mark Lynas urged people to sign a petition demanding full disclosure of the data (only a few hundred have).

But it was a triumph for the scientific and corporate establishment which has used similar tactics to crush other scientists like Arpad Pusztai of the Rowett Institute in Scotland, who was sacked after his research suggested GM potatoes damaged the stomach lining and immune system of rats, and David Quist and Ignacio Chapela, who studied the flow of genes from illegally planted GM maize to Mexican wild maize. But now that the dust is settling, let's look at some of the criticisms and Seralini's responses.

"This is not an innocent scientific publication. The study was designed to produce exactly what was observed," said DrBruce Chassy, professor emeritus of food science at the University of Illinois, who has worked as a consultant for GM companies and has been a member of the US Food and Drug Administration's Food Advisory Council which is fully behind GM.

"Although this paper has been published in a peer-reviewed journal with an [Impact Factor] of about 3, there are anomalies throughout the paper that normally should have been corrected or resolved through the peer-review process," said Maurice Moloney, InsChief Executive of Rothamsted Research.

"The control group is inadequate to make any deduction," said Anthony Trewavas, prominent champion of GM food and a former member of the governing council of Britain's leading plant biotech research organisation, the John Innes Centre.

"We have to ask whether a diet with this level of maize is normal for rats. Another control with an alternative diet should have been included," said Dr Wendy Harwood, senior scientist at the John Innes Centre.

Monsanto was dismissive: "This study does not meet minimum acceptable standards for this type of scientific research, the findings are not supported by the data presented, and the conclusions are not relevant for the purpose of safety assessment."

1. The French researchers were accused of using the Sprague Dawley rat strain which is said to be prone to developing cancers. In response Séralini and his team say these are the same rats as used by Monsanto in the 90-day trials which it used to get authorisation for its maize. This strain of rat has been used in most animal feeding trials to evaluate the safety of GM foods, and their results have long been used by the biotech industry to secure approval to market GM products.

2. The sample size of rats was said to be too small. Séralini responded that six is the OECD recommended protocol for GM food safety toxicology studies and he had based his study on the toxicity part of OECD protocol no. 453. This states that for a cancer trial you need a minimum of 50 animals of each sex per test group but for a toxicity trial a minimum of 10 per sex suffices. Monsanto used 20 rats of each sex per group in its feeding trials but only analysed 10, the same number as Séralini.

3. No data was given about the rats' food intake. Seralini says the rats were allowed to eat as much food as they liked.

4. Séralini has not released the raw data from the trial. In response he says he won't release it until the data underpinning Monsanto's authorisation of NK603 in Europe is also made public.

5. His funding was provided by an anti-biotechnology organisation whose scientific board Séralini heads. But he counters that almost all GM research is funded by corporates or by pro-biotech institutions.

So where does that leave the public?

Despite the concerns over Séralini's methodological flaws, it looks as though the study will not be swept under the carpet. It is the longest study done on this variety of maize and many argue that it must be taken seriously by regulators and governments. French health and safety authorities now plan to investigate NK603 and the study's findings and the European Food Safety Agency has said it will assess the research. Séralini is now demanding that all the data be assessed by an independent international committee, arguing that experts involved in the authorisation of the maize should not be involved.

Equally, the study reopens questions about the regulation of GM crops. There has long been concern that these foods have been evaluated poorly and that the companies have taken advantage of lax regulation. The GM industry, which keeps its own research secret, has resisted investigation or any change.

In fact, there is one irony that a few scientists have pointed out but who have been drowned out in the furore. Séralini's study was not so much about the dangers of GM technology, but the toxicity of the Roundup herbicide used on the crops. Here's Ottoline Leyser, associate director of the Sainsbury Laboratory, University of Cambridge:

"Like most of the GM debate, this work has very little to do with GM. The authors of the paper do not suggest that the effects are caused by genetic modification. They describe effects of the roundup herbicide itself and effects that they attribute to the activity of the enzyme introduced into the roundup resistant maize. There is good evidence that introducing genes into crops using GM techniques results in fewer changes to the crops than introducing them using conventional breeding."

The Council of World Elders is a unification of the best representatives of native tribes, who practice and teach their ancient traditional wisdom for world peace and the healing of our planet.

The members are extraordinarily renowned personalities, who dedicate their lives to the expansion of consciousness of humanity, regeneration of nature and to an integral and conscious treatment of life on Earth.

There will be a world for all people.
There will be a kind new way.
You will feel that beautiful beginning, ? Soon someday ..

Verse 2

As I walked I saw such struggles all around me.
All the broken people wasted on the way.
And I dreamed of how the world might come together, ?soon someday ..

Chorus 1

Tell the people, tell the people.
Tell the people everywhere.
Let them know that we are with them. To make a better world to share.

Chorus 2

Tell the presidents and chairmen.
Tell the lawyers and the kings.
Stand aside if you'd divide us, from the better world we see.
Bridge
There will be. There will be. There will be a world for all people.
Instrumental Break

Chorus 3

No more violence for religion. No more government for greed.
No more poisons where the winds blow. No more children left in need.

Repeat chorus 2

Tell the presidents and chairmen. Tell the lawyers and the kings.
Stand aside if you'd divide us, from the better world we see.

Repeat Verse 3

There will be a world for all people. There will be a kind new way.
You can feel that beautiful beginning, Here today ..

Bridge - repeat 3 times

There will be. There will be. There will be a world for all people.
There will be. There will be. There will be a world for all people.
There will be. There will be. There will be a world for all people. ../fade?

Turmeric, an orange-colored spice imported from India, is part the ginger family and has been a staple in Middle Eastern and Southeast Asian cooking for thousands of years.

In addition, ayurvedic and Chinese medicines utilize turmeric to clear infections and inflammations on the inside and outside of the body. But beyond the holistic health community, Western medical practitioners have only recently come on board in recognizing the benefits of turmeric.

Blocking cancer

Doctors at UCLA recently found that curcumin, the main component in turmeric, appeared to block an enzyme that promotes the growth of head and neck cancer.

In that study, 21 subjects with head and neck cancers chewed two tablets containing 1,000 milligrams of curcumin. An independent lab in Maryland evaluated the results and found that the cancer-promoting enzymes in the patients’ mouths were inhibited by the curcumin and thus prevented from advancing the spread of the malignant cells.

Powerful antioxidant

The University of Maryland’s Medical Center also states that turmeric’s powerful antioxidant properties fight cancer-causing free radicals, reducing or preventing some of the damage they can cause.

While more research is necessary, early studies have indicated that curcumin may help prevent or treat several types of cancer including prostate, skin and colon.

Potent anti-inflammatory

Dr. Randy J. Horwitz, the medical director of the Arizona Center for Integrative Medicine and an assistant professor of clinical medicine at the University of Arizona College of Medicine in Tucson, wrote a paper for the American Academy of Pain Management in which he discussed the health benefits of turmeric.

“Turmeric is one of the most potent natural anti-inflammatories available,” Horwitz states in the paper.

He went on to cite a 2006 University of Arizona study that examined the effect of turmeric on rats with injected rheumatoid arthritis. According to Horwitz, pretreatment with turmeric completely inhibited the onset of rheumatoid arthritis in the rats. In addition, the study found that using turmeric for pre-existing rheumatoid arthritis resulted in a significant reduction of symptoms.

“Raw is best”

Natalie Kling, a Los Angeles-based nutritionist, says she first learned about the benefits of turmeric while getting her degree from the Natural Healing Institute of Neuropathy. “As an anti-inflammatory, antioxidant and antiseptic, it’s a very powerful plant,” she says.

Kling recommends it to clients for joint pain and says that when taken as a supplement, it helps quickly. She advises adding turmeric to food whenever possible and offers these easy tips. “Raw is best,” she said. “Sprinkling it on vegetables or mixing it into dressings is quick and effective.”

If you do cook it, make sure to use a small amount of healthy fat like healthy coconut oil to maximize flavor. Kling also recommends rubbing turmeric on meat and putting it into curries and soups.

“It’s inexpensive, mild in taste, and benefits every system in the body,” Kling says. "Adding this powerful plant to your diet is one of the best things you can do for long term health.”

Following the recent rat study on NK603 GMO corn, Russia has suspended imports of Monsanto corn, while France continues investigations into the possible dangers of GMOs to human health.

On Tuesday this week, Russia suspended the import and use of Monsanto's genetically engineered corn, following the scientific study released on September 19 on rats fed with this corn, which caused serious health problems, including tumors and organ failure.

The study was run over a period of two years, which is the lifetime of the rats being studied and was the first animal feeding trial, set up to study the lifetime effects of exposure to NK603 Roundup tolerant GM maize, and also to Roundup, the world's best-selling herbicide and weedkiller.

According to the peer-reviewed study which was published in the journal Food and Chemical Toxicology and was presented at a news conference in London, the animals on the genetically modified (GM) diet suffered mammary tumors, as well as severe liver and kidney damage.

The Wall Street Journal reports that the consumer-rights watchdog in Russia, Rospotrebnadzor, has said that the country's Institute of Nutrition has been asked to assess the validity of the study.

Rospotrebnadzor has also contacted the European Commission’s Directorate General for Health & Consumers to ask for the EU’s position on the corn’s safety.

After the French study was complete, Monsanto said that it did not think this study would affect its license to export NK603 to Europe, but that they would wait to hear from the European Food Safety Authority (EFSA).

A spokesperson for the company said: "Based on our initial review, we do not believe the study presents information that would justify any change in EFSA’s views on the safety of genetically modified corn products or alter their approval status for genetically modified imports."

Also following the rat feeding study, the French government has called for an investigation into GMOs and has said that it would seek an immediate ban on EU imports, should the findings indicate a detrimental impact of human health. The French Agriculture Minister has asked European authorities to abandon the use of GMO crops.

The French government has asked its health and safety agency to assess the study and had also sent it on to the EFSA.

The French Health, Environment and Farm Ministries said in a joint statement, "Based on the conclusion ..., the government will ask the European authorities to take all necessary measures to protect human and animal health, measures that could go as far as an emergency suspension of imports of NK603 maize in the European Union."

As yet, the US Food and Drug Administration has not reacted to the study.

“There is a giant question mark hanging over these foods and their health risks. For those of us in California, the case for labeling of genetically engineered foods has never been stronger.”

In November of this year, California voters will decide whether to require labeling of genetically engineered foods sold in the state – a requirement which is already in place in 50 other countries.

Monsanto has supported GMO labeling in Europe. One Monsanto advert which ran in the UK read: "Before you buy a potato, or any other food, you may want to know whether it's the product of food biotechnology. We have complete confidence that our food crops are as safe and nutritious as the standard alternatives."

"Recently you may have noticed a label appearing on some of the food in your supermarket. This is to inform you about the use of biotechnology in food. Monsanto fully supports UK food manufacturers and retailers in their introduction of these labels. We believe you should be aware of all the facts before making a purchase."

However, the company is spending millions to defeat the labeling of GMO products in California.

Thursday, September 27, 2012

Campaigning Life Resumes

EPISODE TWENTY SEVEN: “Outer Mongolia”

With the trial over, Helen and Sylvia re-focus their energies on campaigning and decide to surprise RAF Fylingdales by arriving under the cover of darkness to display banners outside the base. It seems, for now, that their humour, wit and cheeky banter has returned as they battle against the unforgiving conditions of the Yorkshire moors to try, once more, to promote their messages of peace.

Clip from the documentary "Fat Head." Guess what? Fat and cholesterol don't cause heart disease. The theory was based on bogus science from the very beginning.

More on this Subject- The Statin Nation Documentary Trailer:

Even More Information - The Cholesterol Scam with Justin Smith

Cholesterol levels in the UK have reduced - but more people are getting heart disease. People with low 'bad' cholesterol are more likely to have heart disease than people with high levels. This clip is an introduction to the cholesterol con.

Wednesday, September 26, 2012

Video by leading Nutrionalist Professor Adam Carey on the subject : 'Benefits of Organic Food'

Adam Carey
Professor Adam Carey is a doctor and nutritionist working on all areas of sports nutrition and human performance. After Oxford, he became an accredited specialist in Obstetrics and Gynaecology with sub-specialist interests in endocrinology and nutrition. He left the NHS in 1998 to actively develop the use of nutritional and lifestyle strategies to improve human performance and reduce the risk of disease through proactive preventative medical management. He is now Visiting Professor in Nutrition at Leeds Metropolitan University. His work in world sports includes posts with the England Rugby Football Union and the England Cricket squad. He has acted as a consultant to the British Olympic Association in the preparation for the 2012 Olympic Games.

The Goliaths of the biotech and processed-food industries have raised $27.2 million to defeat Prop 37, the California Right to Know Genetically Engineered Food Act, and keep you from knowing what's in your food. We can win with much less money. But we do need to raise another $1 million by Sept. 30th to educate voters, distribute leaflets, print signs, saturate the media with the truth about GMOs, and get out the vote.

That's why so many consumers say YES to Proposition 37. It gives us the right to know if there are genetically engineered ingredients in our food ¬ -- with clear information on package labels. That's the very same right consumers in nearly 50 other countries already enjoy.

Riot police have ringed the Spanish parliament in Madrid after clashing with demonstrators as thousands of protesters gather for a march against austerity tagged "Surround Congress". Nine people have been injured and 15 arrested, local media report.

"In 1992 the Food and Drug Administration decided that genetically modified organisms (GMOs) are the functional equivalent of conventional foods. They arrived at this decision without testing GMOs for allergenicity, toxicity, anti-biotic resistance and functional characteristics. As a result hundreds of millions of acres of GMO crops were planted in America without the knowledge or consent of the American people: no safety testing and no long term health studies.

"The FDA has received over a million comments from citizens demanding labeling of GMOs. Ninety percent of Americans agree. So, why no labeling? I'll give you one reason: The influence and the corruption of the political process by Monsanto. Monsanto has been a prime mover in GMO technology, a multi-million dollar GMO lobby here and a major political contributor.

"There is a chance that Monsanto's grip will be broken in California where a GMO labeling initiative is on the ballot. And here in Congress, my legislation HR 3553 will provide for a national labeling law. Americans have a right to know if their food is genetically engineered. It's time for labeling and for people to know how their food is being produced."

Tuesday, September 25, 2012

The doctors prescribing the drugs don't know they don't do what they're meant to. Nor do their patients. The manufacturers know full well, but they're not telling.

Reboxetine is a drug I have prescribed. Other drugs had done nothing for my patient, so we wanted to try something new. I'd read the trial data before I wrote the prescription, and found only well-designed, fair tests, with overwhelmingly positive results. Reboxetine was better than a placebo, and as good as any other antidepressant in head-to-head comparisons. It's approved for use by the Medicines and Healthcare products Regulatory Agency (the MHRA), which governs all drugs in the UK. Millions of doses are prescribed every year, around the world. Reboxetine was clearly a safe and effective treatment. The patient and I discussed the evidence briefly, and agreed it was the right treatment to try next. I signed a prescription.

But we had both been misled. In October 2010, a group of researchers was finally able to bring together all the data that had ever been collected on reboxetine, both from trials that were published and from those that had never appeared in academic papers. When all this trial data was put together, it produced a shocking picture. Seven trials had been conducted comparing reboxetine against a placebo. Only one, conducted in 254 patients, had a neat, positive result, and that one was published in an academic journal, for doctors and researchers to read. But six more trials were conducted, in almost 10 times as many patients. All of them showed that reboxetine was no better than a dummy sugar pill. None of these trials was published. I had no idea they existed.

It got worse. The trials comparing reboxetine against other drugs showed exactly the same picture: three small studies, 507 patients in total, showed that reboxetine was just as good as any other drug. They were all published. But 1,657 patients' worth of data was left unpublished, and this unpublished data showed that patients on reboxetine did worse than those on other drugs. If all this wasn't bad enough, there was also the side-effects data. The drug looked fine in the trials that appeared in the academic literature; but when we saw the unpublished studies, it turned out that patients were more likely to have side-effects, more likely to drop out of taking the drug and more likely to withdraw from the trial because of side-effects, if they were taking reboxetine rather than one of its competitors.

I did everything a doctor is supposed to do. I read all the papers, I critically appraised them, I understood them, I discussed them with the patient and we made a decision together, based on the evidence. In the published data, reboxetine was a safe and effective drug. In reality, it was no better than a sugar pill and, worse, it does more harm than good. As a doctor, I did something that, on the balance of all the evidence, harmed my patient, simply because unflattering data was left unpublished.

Nobody broke any law in that situation, reboxetine is still on the market and the system that allowed all this to happen is still in play, for all drugs, in all countries in the world. Negative data goes missing, for all treatments, in all areas of science. The regulators and professional bodies we would reasonably expect to stamp out such practices have failed us. These problems have been protected from public scrutiny because they're too complex to capture in a soundbite. This is why they've gone unfixed by politicians, at least to some extent; but it's also why it takes detail to explain. The people you should have been able to trust to fix these problems have failed you, and because you have to understand a problem properly in order to fix it, there are some things you need to know.

Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies don't like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug's true effects. Regulators see most of the trial data, but only from early on in a drug's life, and even then they don't give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion.

In their 40 years of practice after leaving medical school, doctors hear about what works ad hoc, from sales reps, colleagues and journals. But those colleagues can be in the pay of drug companies - often undisclosed - and the journals are, too. And so are the patient groups. And finally, academic papers, which everyone thinks of as objective, are often covertly planned and written by people who work directly for the companies, without disclosure. Sometimes whole academic journals are owned outright by one drug company. Aside from all this, for several of the most important and enduring problems in medicine, we have no idea what the best treatment is, because it's not in anyone's financial interest to conduct any trials at all.

Now, on to the details.

In 2010, researchers from Harvard and Toronto found all the trials looking at five major classes of drug - antidepressants, ulcer drugs and so on - then measured two key features: were they positive, and were they funded by industry? They found more than 500 trials in total: 85% of the industry-funded studies were positive, but only 50% of the government-funded trials were. In 2007, researchers looked at every published trial that set out to explore the benefits of a statin. These cholesterol-lowering drugs reduce your risk of having a heart attack and are prescribed in very large quantities. This study found 192 trials in total, either comparing one statin against another, or comparing a statin against a different kind of treatment. They found that industry-funded trials were 20 times more likely to give results favouring the test drug.

These are frightening results, but they come from individual studies. So let's consider systematic reviews into this area. In 2003, two were published. They took all the studies ever published that looked at whether industry funding is associated with pro-industry results, and both found that industry-funded trials were, overall, about four times more likely to report positive results. A further review in 2007 looked at the new studies in the intervening four years: it found 20 more pieces of work, and all but two showed that industry-sponsored trials were more likely to report flattering results.

It turns out that this pattern persists even when you move away from published academic papers and look instead at trial reports from academic conferences. James Fries and Eswar Krishnan, at the Stanford University School of Medicine in California, studied all the research abstracts presented at the 2001 American College of Rheumatology meetings which reported any kind of trial and acknowledged industry sponsorship, in order to find out what proportion had results that favoured the sponsor's drug.

In general, the results section of an academic paper is extensive: the raw numbers are given for each outcome, and for each possible causal factor, but not just as raw figures. The "ranges" are given, subgroups are explored, statistical tests conducted, and each detail is described in table form, and in shorter narrative form in the text. This lengthy process is usually spread over several pages. In Fries and Krishnan (2004), this level of detail was unnecessary. The results section is a single, simple and - I like to imagine - fairly passive-aggressive sentence:

"The results from every randomised controlled trial (45 out of 45) favoured the drug of the sponsor."

How does this happen? How do industry-sponsored trials almost always manage to get a positive result? Sometimes trials are flawed by design. You can compare your new drug with something you know to be rubbish - an existing drug at an inadequate dose, perhaps, or a placebo sugar pill that does almost nothing. You can choose your patients very carefully, so they are more likely to get better on your treatment. You can peek at the results halfway through, and stop your trial early if they look good. But after all these methodological quirks comes one very simple insult to the integrity of the data. Sometimes, drug companies conduct lots of trials, and when they see that the results are unflattering, they simply fail to publish them.

Because researchers are free to bury any result they please, patients are exposed to harm on a staggering scale throughout the whole of medicine. Doctors can have no idea about the true effects of the treatments they give. Does this drug really work best, or have I simply been deprived of half the data? No one can tell. Is this expensive drug worth the money, or has the data simply been massaged? No one can tell. Will this drug kill patients? Is there any evidence that it's dangerous? No one can tell. This is a bizarre situation to arise in medicine, a discipline in which everything is supposed to be based on evidence.

And this data is withheld from everyone in medicine, from top to bottom. Nice, for example, is the National Institute for Health and Clinical Excellence, created by the British government to conduct careful, unbiased summaries of all the evidence on new treatments. It is unable either to identify or to access data on a drug's effectiveness that's been withheld by researchers or companies: Nice has no more legal right to that data than you or I do, even though it is making decisions about effectiveness, and cost-effectiveness, on behalf of the NHS, for millions of people.

In any sensible world, when researchers are conducting trials on a new tablet for a drug company, for example, we'd expect universal contracts, making it clear that all researchers are obliged to publish their results, and that industry sponsors - which have a huge interest in positive results - must have no control over the data. But, despite everything we know about industry-funded research being systematically biased, this does not happen. In fact, the opposite is true: it is entirely normal for researchers and academics conducting industry-funded trials to sign contracts subjecting them to gagging clauses that forbid them to publish, discuss or analyse data from their trials without the permission of the funder.

This is such a secretive and shameful situation that even trying to document it in public can be a fraught business. In 2006, a paper was published in the Journal of the American Medical Association (Jama), one of the biggest medical journals in the world, describing how common it was for researchers doing industry-funded trials to have these kinds of constraints placed on their right to publish the results. The study was conducted by the Nordic Cochrane Centre and it looked at all the trials given approval to go ahead in Copenhagen and Frederiksberg. (If you're wondering why these two cities were chosen, it was simply a matter of practicality: the researchers applied elsewhere without success, and were specifically refused access to data in the UK.) These trials were overwhelmingly sponsored by the pharmaceutical industry (98%) and the rules governing the management of the results tell a story that walks the now familiar line between frightening and absurd.

For 16 of the 44 trials, the sponsoring company got to see the data as it accumulated, and in a further 16 it had the right to stop the trial at any time, for any reason. This means that a company can see if a trial is going against it, and can interfere as it progresses, distorting the results. Even if the study was allowed to finish, the data could still be suppressed: there were constraints on publication rights in 40 of the 44 trials, and in half of them the contracts specifically stated that the sponsor either owned the data outright (what about the patients, you might say?), or needed to approve the final publication, or both. None of these restrictions was mentioned in any of the published papers.

When the paper describing this situation was published in Jama, Lif, the Danish pharmaceutical industry association, responded by announcing, in the Journal of the Danish Medical Association, that it was "both shaken and enraged about the criticism, that could not be recognised". It demanded an investigation of the scientists, though it failed to say by whom or of what. Lif then wrote to the Danish Committee on Scientific Dishonesty, accusing the Cochrane researchers of scientific misconduct. We can't see the letter, but the researchers say the allegations were extremely serious - they were accused of deliberately distorting the data - but vague, and without documents or evidence to back them up.

Nonetheless, the investigation went on for a year. Peter Gøtzsche, director of the Cochrane Centre, told the British Medical Journal that only Lif's third letter, 10 months into this process, made specific allegations that could be investigated by the committee. Two months after that, the charges were dismissed. The Cochrane researchers had done nothing wrong. But before they were cleared, Lif copied the letters alleging scientific dishonesty to the hospital where four of them worked, and to the management organisation running that hospital, and sent similar letters to the Danish medical association, the ministry of health, the ministry of science and so on. Gøtzsche and his colleagues felt "intimidated and harassed" by Lif's behaviour. Lif continued to insist that the researchers were guilty of misconduct even after the investigation was completed.

Paroxetine is a commonly used antidepressant, from the class of drugs known as selective serotonin reuptake inhibitors or SSRIs. It's also a good example of how companies have exploited our long-standing permissiveness about missing trials, and found loopholes in our inadequate regulations on trial disclosure.

To understand why, we first need to go through a quirk of the licensing process. Drugs do not simply come on to the market for use in all medical conditions: for any specific use of any drug, in any specific disease, you need a separate marketing authorisation. So a drug might be licensed to treat ovarian cancer, for example, but not breast cancer. That doesn't mean the drug doesn't work in breast cancer. There might well be some evidence that it's great for treating that disease, too, but maybe the company hasn't gone to the trouble and expense of getting a formal marketing authorisation for that specific use. Doctors can still go ahead and prescribe it for breast cancer, if they want, because the drug is available for prescription, it probably works, and there are boxes of it sitting in pharmacies waiting to go out. In this situation, the doctor will be prescribing the drug legally, but "off-label".

Now, it turns out that the use of a drug in children is treated as a separate marketing authorisation from its use in adults. This makes sense in many cases, because children can respond to drugs in very different ways and so research needs to be done in children separately. But getting a licence for a specific use is an arduous business, requiring lots of paperwork and some specific studies. Often, this will be so expensive that companies will not bother to get a licence specifically to market a drug for use in children, because that market is usually much smaller.

So it is not unusual for a drug to be licensed for use in adults but then prescribed for children. Regulators have recognised that this is a problem, so recently they have started to offer incentives for companies to conduct more research and formally seek these licences.

When GlaxoSmithKline applied for a marketing authorisation in children for paroxetine, an extraordinary situation came to light, triggering the longest investigation in the history of UK drugs regulation. Between 1994 and 2002, GSK conducted nine trials of paroxetine in children. The first two failed to show any benefit, but the company made no attempt to inform anyone of this by changing the "drug label" that is sent to all doctors and patients. In fact, after these trials were completed, an internal company management document stated: "It would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine." In the year after this secret internal memo, 32,000 prescriptions were issued to children for paroxetine in the UK alone: so, while the company knew the drug didn't work in children, it was in no hurry to tell doctors that, despite knowing that large numbers of children were taking it. More trials were conducted over the coming years - nine in total - and none showed that the drug was effective at treating depression in children.

It gets much worse than that. These children weren't simply receiving a drug that the company knew to be ineffective for them; they were also being exposed to side-effects. This should be self-evident, since any effective treatment will have some side-effects, and doctors factor this in, alongside the benefits (which in this case were nonexistent). But nobody knew how bad these side-effects were, because the company didn't tell doctors, or patients, or even the regulator about the worrying safety data from its trials. This was because of a loophole: you have to tell the regulator only about side-effects reported in studies looking at the specific uses for which the drug has a marketing authorisation. Because the use of paroxetine in children was "off-label", GSK had no legal obligation to tell anyone about what it had found.

People had worried for a long time that paroxetine might increase the risk of suicide, though that is quite a difficult side-effect to detect in an antidepressant. In February 2003, GSK spontaneously sent the MHRA a package of information on the risk of suicide on paroxetine, containing some analyses done in 2002 from adverse-event data in trials the company had held, going back a decade. This analysis showed that there was no increased risk of suicide. But it was misleading: although it was unclear at the time, data from trials in children had been mixed in with data from trials in adults, which had vastly greater numbers of participants. As a result, any sign of increased suicide risk among children on paroxetine had been completely diluted away.

Later in 2003, GSK had a meeting with the MHRA to discuss another issue involving paroxetine. At the end of this meeting, the GSK representatives gave out a briefing document, explaining that the company was planning to apply later that year for a specific marketing authorisation to use paroxetine in children. They mentioned, while handing out the document, that the MHRA might wish to bear in mind a safety concern the company had noted: an increased risk of suicide among children with depression who received paroxetine, compared with those on dummy placebo pills.

This was vitally important side-effect data, being presented, after an astonishing delay, casually, through an entirely inappropriate and unofficial channel. Although the data was given to completely the wrong team, the MHRA staff present at this meeting had the wit to spot that this was an important new problem. A flurry of activity followed: analyses were done, and within one month a letter was sent to all doctors advising them not to prescribe paroxetine to patients under the age of 18.

How is it possible that our systems for getting data from companies are so poor, they can simply withhold vitally important information showing that a drug is not only ineffective, but actively dangerous? Because the regulations contain ridiculous loopholes, and it's dismal to see how GSK cheerfully exploited them: when the investigation was published in 2008, it concluded that what the company had done - withholding important data about safety and effectiveness that doctors and patients clearly needed to see - was plainly unethical, and put children around the world at risk; but our laws are so weak that GSK could not be charged with any crime.

After this episode, the MHRA and EU changed some of their regulations, though not adequately. They created an obligation for companies to hand over safety data for uses of a drug outside its marketing authorisation; but ridiculously, for example, trials conducted outside the EU were still exempt. Some of the trials GSK conducted were published in part, but that is obviously not enough: we already know that if we see only a biased sample of the data, we are misled. But we also need all the data for the more simple reason that we need lots of data: safety signals are often weak, subtle and difficult to detect. In the case of paroxetine, the dangers became apparent only when the adverse events from all of the trials were pooled and analysed together.

That leads us to the second obvious flaw in the current system: the results of these trials are given in secret to the regulator, which then sits and quietly makes a decision. This is the opposite of science, which is reliable only because everyone shows their working, explains how they know that something is effective or safe, shares their methods and results, and allows others to decide if they agree with the way in which the data was processed and analysed. Yet for the safety and efficacy of drugs, we allow it to happen behind closed doors, because drug companies have decided that they want to share their trial results discretely with the regulators. So the most important job in evidence-based medicine is carried out alone and in secret. And regulators are not infallible, as we shall see.

Rosiglitazone was first marketed in 1999. In that first year, Dr John Buse from the University of North Carolina discussed an increased risk of heart problems at a pair of academic meetings. The drug's manufacturer, GSK, made direct contact in an attempt to silence him, then moved on to his head of department. Buse felt pressured to sign various legal documents. To cut a long story short, after wading through documents for several months, in 2007 the US Senate committee on finance released a report describing the treatment of Buse as "intimidation".

But we are more concerned with the safety and efficacy data. In 2003 the Uppsala drug monitoring group of the World Health Organisation contacted GSK about an unusually large number of spontaneous reports associating rosiglitazone with heart problems. GSK conducted two internal meta-analyses of its own data on this, in 2005 and 2006. These showed that the risk was real, but although both GSK and the FDA had these results, neither made any public statement about them, and they were not published until 2008.

During this delay, vast numbers of patients were exposed to the drug, but doctors and patients learned about this serious problem only in 2007, when cardiologist Professor Steve Nissen and colleagues published a landmark meta-analysis. This showed a 43% increase in the risk of heart problems in patients on rosiglitazone. Since people with diabetes are already at increased risk of heart problems, and the whole point of treating diabetes is to reduce this risk, that finding was big potatoes. Nissen's findings were confirmed in later work, and in 2010 the drug was either taken off the market or restricted, all around the world.

Now, my argument is not that this drug should have been banned sooner because, as perverse as it sounds, doctors do often need inferior drugs for use as a last resort. For example, a patient may develop idiosyncratic side-effects on the most effective pills and be unable to take them any longer. Once this has happened, it may be worth trying a less effective drug if it is at least better than nothing.

The concern is that these discussions happened with the data locked behind closed doors, visible only to regulators. In fact, Nissen's analysis could only be done at all because of a very unusual court judgment. In 2004, when GSK was caught out withholding data showing evidence of serious side-effects from paroxetine in children, their bad behaviour resulted in a US court case over allegations of fraud, the settlement of which, alongside a significant payout, required GSK to commit to posting clinical trial results on a public website.

Nissen used the rosiglitazone data, when it became available, and found worrying signs of harm, which they then published to doctors - something the regulators had never done, despite having the information years earlier. If this information had all been freely available from the start, regulators might have felt a little more anxious about their decisions but, crucially, doctors and patients could have disagreed with them and made informed choices. This is why we need wider access to all trial reports, for all medicines.

Missing data poisons the well for everybody. If proper trials are never done, if trials with negative results are withheld, then we simply cannot know the true effects of the treatments we use. Evidence in medicine is not an abstract academic preoccupation. When we are fed bad data, we make the wrong decisions, inflicting unnecessary pain and suffering, and death, on people just like us.

Major Victory for Quebec Students, Environmental Activists

by Richard Fidler

Global Research Canada, 24 September 2012

Their demonstrations have shaken Quebec in recent months, and on September 20th students and environmentalists won major victories.

At her first news conference as premier, Pauline Marois announced that her Parti Québécois government had cancelled the university tuition fees increase imposed by the Charest Liberal government, and would repeal the repressive provisions of Law 12 (formerly Bill 78)

Charest had imposed in his efforts to smash the province’s massive student strike. Among other things, this will remove the restrictions on public demonstrations and the threat of decertification of student associations.

In addition, Marois has ordered the closing of Gentilly-2, Quebec’s only nuclear reactor, while promising funding to promote economic diversification to offset job losses resulting from the shutdown. And she will proceed with her promise to cancel a $58-million government loan to reopen the Jeffrey Mine, Quebec’s last asbestos mining operation.

The new Natural Resources minister, Martine Ouellet, followed up by announcing an end to shale gas exploration and development in Quebec. “I do not see the day when there will be technologies that will allow their safe development,” she said. Residents of dozens of Quebec communities have been mobilizing against shale gas. As of March, there were 31 wells already drilled, and 18 had been fracked. The shale gas industry, which has spent some $200-million to date in Quebec, had plans to dig up to 600 wells a year by 2015.

A former president of Eau Secours!, a water protection group, Ouellet is one of three new ministers with strong environmentalist credentials, the others being Environment minister Daniel Breton, a co-founder of the Parti Vert, the Green party, and his deputy Scott McKay, a former Montréal city councillor and one-time leader of the Greens.

Student leaders were jubilant at the cancellation of the tuition fees increase. “Bravo to the striking students,” tweeted Gabriel Nadeau-Dubois, the former co-spokesman for the CLASSE, the most militant of the student groups that led the unprecedented four-month student strike in Quebec’s “printemps érable.”

“Total Victory” for Students

“It’s a total victory!” said Martine Desjardins, president of the FEUQ, the university students’ federation. “Sept. 20 will be etched in the annals of history in Quebec,” tweeted the FECQ, the college students’ federation. The students also welcomed Marois’ announcement that her government would maintain the $39-million boost to financial assistance introduced by the Liberals to offset their tuition increase.

The PQ government is committed to holding a summit on education as early as this fall to debate and propose new arrangements for funding higher education in Quebec. Marois says she will be defending her party’s proposal to index tuition fee increases, which she says amounts to a freeze on current levels. The CLASSE pledged that it will continue to fight for free tuition, as did Québec solidaire.

Marois also announced cancellation of the $200 per person health tax imposed by Charest, which would have brought almost a billion dollars into the government coffers. The loss of this user fee will be made up by a tax increase on incomes over $130,000 a year and a 25 percentage point decrease in the capital gains exemption, she said.

Marois also confirmed her determination to bring in a balanced budget by 2014, which means that these popular decisions will no doubt be followed by major cutbacks in spending in other areas, yet unspecified.
However, it was a good day for the new Parti Québécois government. Predictably, it was met by cynical reactions in the capitalist media. Typical were the editors of the Montreal Gazette, who expressed the hope that the right-wing opposition parties would come up with what they described, in a mixture of hope and prediction, as “a persuasive alternative to what might probably be the shambles of PQ governance.”[1]

In a more sombre vein, Le Devoir‘s environment columnist Louis-Gilles Francoeur drew attention to the powerful business interests who will be quick to campaign against even modest efforts that threaten their profits.

“The lobbies that profit from the lack of rules governing wetlands, for example, have already claimed the head of Thomas Mulcair, then Environment minister.[2]The review of [Charest's] Plan Nord and the changes that will be made by minister Ouellet – to whom we owe some caustic analyses of the proposed overhaul of the Mining Act – will no doubt provoke a groundswell of protest from the major investors… for whom the green economy is still an irritant and not a potential.

“Then we will see whether minister Breton took his dreams for reality when he declared that the greens were now in power….” •

Richard Fidler is an Ottawa member of the Socialist Project. This article first appeared on his blogLife on the Left.

About Me

An American living in Sweden.
**PRIVACY NOTICE:
Warning--any person and/or institution and/or Agent and/or Agency of any governmental structure including but not limited to ALL Governments or private mediums or corporations or individuals also using or monitoring/using this website or any of its associated websites, you do NOT have my permission to utilize any of my profile information nor any of the content contained herein including, but not limited to my photos, and/ or the comments made about my photo's or any other "picture" art posted on my profile. You are hereby notified that you are strictly prohibited from disclosing, copying, distributing, disseminating, or taking any other action against me with regard to this profile and the contents herein. The foregoing prohibitions also apply to your employee(s), agent(s), student(s) or any personnel under your direction or control. The contents of this profile are private and legally privileged and confidential information, and the violation of my personal privacy is punishable by law and will be strictly enforced.